International Publication No. WO 95/20595, and U.S. Pat. Nos. 5,587,362; 5,567,688; and 5,565,438 disclose L-FMAU and derivatives of formula (2): in which R′ represents purine or pyrimidine base; and
R″ represents hydrogen, acyl, alkyl, monophosphate, diphosphate or triphosphate.
Nucleoside compounds of formula (2) exhibit anti-viral activity against HBV and EBV. Among these nucleoside compounds, L-FMAU shows particularly potent anti-viral activity against HBV and EBV with very low cytotoxicity and is, therefore, preferred as an anti-viral agent. Nucleoside compounds of formula (2), including L-FMAU, are useful in the prevention and treatment of HBV infections and related conditions, such as anti-HBV antibody positive and HBV-positive conditions, chronic liver inflammation caused by HBV, cirrhosis, acute hepatitis, fulminant hepatitis, chronic persistent hepatitis, and fatigue. In addition, they can also be used for the treatment of EBV-associated disorders.
According to the method disclosed in International Publication No. WO 95/20595, L-FMAU of formula (1) may be prepared using L-xylose of formula (3) as a starting material: L-xylose of formula (3) cannot be obtained from natural substances and must therefore be produced by synthetic methods. When L-xylose is used as the starting material, the production cost of L-FMAU is therefore very high.
It has now been discovered that L-FMAU can be economically prepared from L-arabinose, which is present in many natural substances and, thus, is an inexpensive starting material, thereby completing the present invention.